Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia—Relevance for Mental Diseases
Cells July 27, 2021 Dasiel O. Borroto‐escuela, Patrizia Ambrogini, Manuel Narváez et al. 29 citations
Heteroreceptor complexes represent a new biological principle for signal integration in the brain, with bidirectional allosteric receptor–receptor interactions offering novel targets for treating CNS diseases, including mental disorders. The existence of D2R-5-HT2AR heterocomplexes can explain the anti-schizophrenic effects of atypical antipsychotics through blocking the allosteric enhancement of D2R signaling by 5-HT2AR activation. This principle also helps understand mechanisms of 5-HT hallucinogens like psilocybin and the prosocial, anti-stress actions of MDMA. GalR1-GalR2 heterodimers and putative GalR1-GalR2-5-HT1 complexes are targets for galanin fragment Gal(1–15) in modulating emotional networks. Antidepressant drugs, including TCAs, SSRIs, and ketamine, can directly bind to the TrkB receptor, providing a novel mechanism for their actions. Astrocytes and their allosteric receptor–receptor interactions in modulating forebrain glutamate synapses are relevant to major depressive disorder research.